A backbone of chiral γ-secondary amino alcohol is widely found in various drug molecules and physiologically-active molecules, such as, Duloxetine, Fluoxetine or the like. Duloxetine hydrochloride, chemically named as (S)-N-methyl-3-(1-naphthoxy)-3-(2-thienyl)-1-propylamine hydrochloride, is a reuptake inhibitor against 5-hydroxytryptamine and norepinephrine developed by Eli Lilly and Company (USA), and is clinically applied mainly for treatment of depressive disorder and anxiety. Its global sale of about 5 billions U.S. dollars in the year of 2013 shows a remarkably massive market. Recently, the patent for this drug is to expire, and some drug manufacturers have been approved for its production.
Currently, a chiral γ-secondary amino alcohol is mainly obtained by the means of racemic resolution. However, the traditional resolution technology has a yield of less than 50% and a considerable proportion of isomer is difficult to use, which causes an increase in cost as well as environmental pollution. Synthesis of γ-amino alcohol with asymmetric hydrogenation technology is less studied up to now. In 1991, Professor Achiwa for the first time reported asymmetric synthesis of γ-secondary amino alcohol by catalytic hydrogenation of β-secondary amino ketone using (2S, 4S)-MCCPM as a catalyst, giving an ee value of 90.8% (a) S. Sakuraba, K. Achiwa, Synlett 1991, 689; b) S. Sakuraba, K. Achiwa, Chem. Pharm. Bull. 1995, 43, 748). In 2005, Professor Xumu Zhang reported catalytic asymmetric hydrogenation of β-secondary amino ketone as a substrate using DuanPhos-Rh as a catalyst, giving an ee value as high as 99% and TON of higher than 4500 (D. Liu, W. Gao, C. Wang, X. Zhang, Angew. Chem. Int. Ed. 2005, 44, 1687).
However, in the prior art, inactivation of catalyst caused by the chiral γ-secondary amino alcohol product, which is due to the strong coordination of the nitrogen atom, and instability of the substrate β-secondary amino ketone, makes it difficult to conduct asymmetric hydrogenation of β-secondary amino ketone. Additionally, in the prior art, the chiral γ-secondary amino alcohol has been synthesized by a longer route, and resolution requires a resolving agent, which is expensive and leads to a corrosivity problem to some degree.